Silicone hydrogel lens with a crosslinked hydrophilic coating

ABSTRACT

The invention is related to a cost-effective method for making a silicone hydrogel contact lens having a crosslinked hydrophilic coating thereon. A method of the invention involves autoclaving, in a sealed lens package, a silicone hydrogel contact lens having a base coating of polyacrylic acid thereon in an aqueous solution in the presence of a water-soluble, crosslinkable hydrophilic polymeric material having epoxide groups, for a period of time sufficient to covalently attach the crosslinkable hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through covalent linkages each formed between one epoxide group and one of the carboxyl groups on and/or near the surface of the silicone hydrogel contact lens.

This application claims the benefits under 35 USC §119 (e) of U.S.provisional application No. 61/560,103 filed Nov. 15, 2011, incorporatedby reference in its entirety.

The present invention generally relates to a cost-effective andtime-efficient method for applying a crosslinked hydrophilic coatingonto a silicone hydrogel contact lens to improve its hydrophilicity andlubricity. In addition, the present invention provides an ophthalmiclens product.

BACKGROUND

Soft silicone hydrogel contact lenses are increasingly becoming popularbecause of their high oxygen permeability and comfort. But, a siliconehydrogel material typically has a surface, or at least some areas of itssurface, which is hydrophobic (non-wettable) and susceptible toadsorbing lipids or proteins from the ocular environment and may adhereto the eye. Thus, a silicone hydrogel contact lens will generallyrequire a surface modification.

A known approach for modifying the hydrophilicity of a relativelyhydrophobic contact lens material is through the use of a plasmatreatment, for example, commercial lenses such as Focus NIGHT & DAY™ andO2OPTIX™ (CIBA VISION), and PUREVISION™ (Bausch & Lomb) utilize thisapproach in their production processes. Advantages of a plasma coating,such as, e.g., those may be found with Focus NIGHT & DAY™, are itsdurability, relatively high hydrophilicity/wettability), and lowsusceptibility to lipid and protein deposition and adsorption. But,plasma treatment of silicone hydrogel contact lenses may not be costeffective, because the preformed contact lenses must typically be driedbefore plasma treatment and because of relative high capital investmentassociated with plasma treatment equipment.

Another approach for modifying the surface hydrophilicity of a siliconehydrogel contact lens is the incorporation of wetting agents(hydrophilic polymers) into a lens formulation for making the siliconehydrogel contact lens as proposed in U.S. Pat. Nos. 6,367,929,6,822,016, 7,052,131, and 7,249,848. This method may not requireadditional posterior processes for modifying the surface hydrophilicityof the lens after cast-molding of silicone hydrogel contact lenses.However, wetting agents may not be compatible with the siliconecomponents in the lens formulation and the incompatibility may imparthaziness to the resultant lenses. Further, such surface treatment may besusceptible to lipid deposition and adsorption. In addition, suchsurface treatment may not provide a durable surface for extended wearpurposes.

A further approach for modifying the hydrophilicity of a relativelyhydrophobic contact lens material is a layer-by-layer (LbL) polyionicmaterial deposition technique (see for example, U.S. Pat. Nos.6,451,871, 6,717,929, 6,793,973, 6,884,457, 6,896,926, 6,926,965,6,940,580, and 297,725, and U.S. Patent Application Publication Nos. US200710229758A1, US 200810174035A1, and US 2008/0152800A1). Although theLbL deposition technique can provide a cost effective process forrendering a silicone hydrogel material wettable, LbL coatings may not beas durable as plasma coatings and may have relatively high densities ofsurface charges; which may interfere with contact lens cleaning anddisinfecting solutions. To improve the durability, crosslinking of LbLcoatings on contact lenses has been proposed in commonly-owned copendingUS patent application publication Nos. 2008/0226922 A1 and 2009/0186229A1 (incorporated by reference in their entireties). However, crosslinkedLbL coatings may have a hydrophilicity and/or wettability inferior thanoriginal LbL coatings (prior to crosslinking) and still have relativehigh densities of surface charges.

A still further approach for modifying the hydrophilicity of arelatively hydrophobic contact lens material is to attach hydrophilicpolymers onto contact lenses according to various mechanisms (see forexample, U.S. Pat. Nos. 6,099,122, 6,436,481, 6,440,571, 6,447,920,6,465,056, 6,521,352, 6,586,038, 6,623,747, 6,730,366, 6,734,321,6,835,410, 6,878,399, 6,923,978, 6,440,571, and 6,500,481, US PatentApplication Publication Nos. 2009/0145086 A1, 2009/0145091A1,2008/0142038A1, and 2007/0122540A1, all of which are herein incorporatedby reference in their entireties). Although those techniques can be usein rendering a silicone hydrogel material wettable, they may not becost-effective and/or time-efficient for implementation in a massproduction environment, because they typically require relatively longtime and/or involve laborious, multiple steps to obtain a hydrophiliccoating.

Therefore, there is still a need for a method of producing siliconehydrogel contact lenses with wettable and durable coating (surface) in acost-effective and time-efficient manner.

SUMMARY OF THE INVENTION

The invention, in one aspect, provides a method for producing siliconehydrogel contact lenses each having a crosslinked hydrophilic coatingthereon, the method of invention comprising the steps of: (a) obtaininga silicone hydrogel contact lens; (b) applying a layer ofcarboxyl-containing polymeric material onto the silicone hydrogelcontact lens; (c) placing the silicone hydrogel contact lens with thelayer of carboxyl-containing polymeric material thereon into a lenspackage containing a packaging solution, wherein the packaging solutioncomprises one or more crosslinkable hydrophilic polymeric materialsselected from the group consisting of (i) a water-soluble hydrophilicpolymer polymeric material having epoxide groups, wherein thehydrophilic polymeric material is partial reaction product of a firstmulti-arm polyethyleneglycol having terminal epoxide groups and a firsthydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,hydroxyl group, thiol group, and combination thereof, (ii) a secondmulti-arm polyethyleneglycol having terminal epoxide groups, (iii) amixture of a third multi-arm polyethyleneglycol having terminal epoxidegroups and a second hydrophilicity-enhancing agent having at least onereactive functional group selected from the group consisting of aminogroup, carboxyl group, hydroxyl group, thiol group, and combinationthereof, and (iv) a combination thereof; (d) sealing the package; (e)autoclaving the sealed package with the silicone hydrogel contact lenstherein at a temperature from about 115° C. to about 125° C. for atleast about twenty minutes, thereby forming a non-silicone hydrogelcoating on the silicone hydrogel contact lens, wherein the non-siliconehydrogel coating is a crosslinked polymeric material composed of thecarboxyl-containing polymeric material crosslinked with the one or morecrosslinkable material.

In another aspect, the invention provides a silicone hydrogel contactlens obtained according to a method of the invention, wherein thesilicone hydrogel contact lens has an oxygen permeability of at leastabout 40 barrers, a surface wettability characterized by a water contactangle of about 100 degrees or less, and a good coating durabilitycharacterized by surviving a digital rubbing test.

These and other aspects of the invention will become apparent from thefollowing description of the presently preferred embodiments. Thedetailed description is merely illustrative of the invention and doesnot limit the scope of the invention, which is defined by the appendedclaims and equivalents thereof. As would be obvious to one skilled inthe art, many variations and modifications of the invention may beeffected without departing from the spirit and scope of the novelconcepts of the disclosure.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Reference now will be made in detail to the embodiments of theinvention. It will be apparent to those skilled in the art that variousmodifications, variations and combinations can be made in the presentinvention without departing from the scope or spirit of the invention.For instance, features illustrated or described as part of oneembodiment, can be used on another embodiment to yield a still furtherembodiment. Thus, it is intended that the present invention cover suchmodifications, variations and combinations as come within the scope ofthe appended claims and their equivalents. Other objects, features andaspects of the present invention are disclosed in or are obvious fromthe following detailed description. It is to be understood by one ofordinary skill in the art that the present discussion is a descriptionof exemplary embodiments only, and is not intended as limiting thebroader aspects of the present invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Generally, the nomenclatureused herein and the laboratory procedures are well known and commonlyemployed in the art. Conventional methods are used for these procedures,such as those provided in the art and various general references. Wherea term is provided in the singular, the inventors also contemplate theplural of that term. The nomenclature used herein and the laboratoryprocedures described below are those well known and commonly employed inthe art.

A “silicone hydrogel contact lens” refers to a contact lens comprising asilicone hydrogel material.

A “hydrogel” refers to a crosslinked polymeric material which is notwater-soluble and contains at least 10% by weight of water within itspolymer matrix when fully hydrated. A “silicone hydrogel” refers to asilicone-containing hydrogel. A “non-silicone hydrogel” refers to ahydrogel that is free of silicone.

A “crosslinked coating” or “hydrogel coating” as used in thisapplication means a crosslinked polymeric material having athree-dimensional network that can contain water when fully hydrated.The three-dimensional network of a crosslinked polymeric material can beformed by crosslinking of two or more linear or branched polymersthrough crosslinkages.

A “vinylic monomer”, as used herein, refers to a compound that has onesole ethylenically unsaturated group and can be polymerized actinicallyor thermally.

The term “olefinically unsaturated group” or “ethylenically unsaturatedgroup” is employed herein in a broad sense and is intended to encompassany groups containing at least one >C═C< group. Exemplary ethylenicallyunsaturated groups include without limitation (meth)acryloyl

allyl, vinyl

styrenyl, or other C═C containing groups.

The term “(meth)acrylamide” refers to methacrylamide and/or acrylamide.

The term “(meth)acrylate” refers to methacrylate and/or acrylate.

A “hydrophilic vinylic monomer”, as used herein, refers to a vinylicmonomer which as a homopolymer typically yields a polymer that iswater-soluble or can absorb at least 10 percent by weight water whenfully hydrated.

A “hydrophobic vinylic monomer”, as used herein, refers to a vinylicmonomer which as a homopolymer typically yields a polymer that isinsoluble in water and can absorb less than 10 percent by weight water.

A “macromer” or “prepolymer” refers to a medium and high molecularweight compound or polymer that contains two or more ethylenicallyunsaturated groups. Medium and high molecular weight typically meansaverage molecular weights greater than 700 Daltons.

A “crosslinker” refers to a compound having at least two ethylenicallyunsaturated groups. A “crosslinking agent” refers to a crosslinkerhaving a molecular weight of about 700 Daltons or less.

A “polymer” means a material formed by polymerizing/crosslinking one ormore monomers or macromers or prepolymers.

“Molecular weight” of a polymeric material (including monomeric ormacromeric materials), as used herein, refers to the weight-averagemolecular weight unless otherwise specifically noted or unless testingconditions indicate otherwise.

A “multi-arm polyethylene glycol” means a polymeric material composed ofa branched core and arms each essentially made of polyethylene glycolchains.

The term “amino group” refers to a primary or secondary amino group offormula —NHR′, where R′ is hydrogen or a C₁-C₂₀ unsubstituted orsubstituted, linear or branched alkyl group, unless otherwisespecifically noted.

The term “phosphorylcholine” refers to a zwitterionic group of

in which n is an integer of 1 to 5 and R₁, R₂ and R₃ independently ofeach other are C₁-C₈ alkyl or C₁-C₈ hydroxyalkyl.

The term “reactive vinylic monomer” refers to a vinylic monomer having acarboxyl group or an amino group (i.e., a primary or secondary aminogroup).

The term “non-reactive hydrophilic vinylic monomer” refers to ahydrophilic vinylic monomer which is free of any carboxyl group or aminogroup (i.e., primary or secondary amino group). A non-reactive vinylicmonomer can include a tertiary or quaternium amino group.

The term “water-soluble” in reference to a polymer means that thepolymer can be dissolved in water to an extent sufficient to form anaqueous solution of the polymer having a concentration of up to about30% by weight at room temperature (defined above).

A “water contact angle” refers to an average water contact angle (i.e.,contact angles measured by Sessile Drop method), which is obtained byaveraging measurements of contact angles with at least 3 individualcontact lenses.

The term “intactness” in reference to a coating on a SiHy contact lensis intended to describe the extent to which the contact lens can bestained by Sudan Black in a Sudan Black staining test described inExample 1. Good intactness of the coating on a SiHy contact lens meansthat there is practically no Sudan Black staining of the contact lens.

The term “durability” in reference to a coating on a SiHy contact lensis intended to describe that the coating on the SiHy contact lens cansurvive a digital rubbing test.

The intrinsic “oxygen permeability”, Dk, of a material is the rate atwhich oxygen will pass through a material. In accordance with theinvention, the term “oxygen permeability (Dk)” in reference to ahydrogel (silicone or non-silicone) or a contact lens means an oxygenpermeability (Dk) which is corrected for the surface resistance tooxygen flux caused by the boundary layer effect according to theprocedures shown in Examples hereinafter. Oxygen permeability isconventionally expressed in units of barrers, where “barrer” is definedas [(cm³ oxygen)(mm)/(cm²)(sec)(mm Hg)]×10⁻¹⁰.

The “oxygen transmissibility”, Dk/t, of a lens or material is the rateat which oxygen will pass through a specific lens or material with anaverage thickness of t [in units of mm] over the area being measured.Oxygen transmissibility is conventionally expressed in units ofbarrers/mm, where “barrers/mm” is defined as [(cm³ oxygen)/(cm²)(sec)(mmHg)]×10⁻⁹.

The “ion permeability” through a lens correlates with the lonofluxDiffusion Coefficient. The lonoflux Diffusion Coefficient, D (in unitsof [mm²/min]), is determined by applying Fick's law as follows:D=−n′/(A×dc/dx)where n′=rate of ion transport [mol/min]; A=area of lens exposed [mm²];dc=concentration difference [mol/L]; dx=thickness of lens [mm].

“Ophthalmically compatible”, as used herein, refers to a material orsurface of a material which may be in intimate contact with the ocularenvironment for an extended period of time without significantlydamaging the ocular environment and without significant user discomfort.

The term “ophthalmically safe” with respect to a packaging solution forsterilizing and storing contact lenses is meant that a contact lensstored in the solution is safe for direct placement on the eye withoutrinsing after autoclave and that the solution is safe and sufficientlycomfortable for daily contact with the eye via a contact lens. Anophthalmically-safe packaging solution after autoclave has a tonicityand a pH that are compatible with the eye and is substantially free ofocularly irritating or ocularly cytotoxic materials according tointernational ISO standards and U.S. FDA regulations.

The invention is generally directed to a cost-effective andtime-efficient method for making silicone hydrogel contact lenses withdurable non-silicone hydrogel coatings by use of a water-soluble andcrosslinkable hydrophilic polymeric material having epoxide groups. Theinvention is partly based on the surprising discoveries that awater-soluble, epoxy-containing multi-arm poly(ethylene glycol) or awater-soluble, epoxy-containing hydrophilic polymeric material which isa partial reaction product of a water-soluble, epoxy-containingmulti-arm poly(ethylene glycol) with at least onehydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,hydroxyl group, thiol group, and combination thereof, can be used toform a non-silicone hydrogel coating with a good surface hydrophilicityand/or wettability, a good hydrophilicity and a good intactness on asilicone hydrogel contact lens having carboxyl acid and/or amino groupsat or near its surface, during the sterilization (i.e., autoclave) stepof contact lens product. At the temperature of autoclave (from 110 to130° C.), epoxide groups react with functional groups such as aminogroups, thiol groups, carboxyl groups —COOH, and/or hydroxyl groups toform neutral, hydroxyl-containing covalent linkages. Those epoxidegroups that do not participate in crosslinking reactions can behydrolyzed during autoclave. It is believed that a multi-armpolyethyleneglycol with terminal epoxide groups can ensure resultanthydrogel coating to have a relatively low crosslinking density (or aloose 3-dimensional structure with dangling polymer chains and/or chainsegments that may impart a good surface hydrophilicity, wettabilityand/or lubricity to the contact lenses.

By using the method of the invention, the coating process can becombined with the sterilization step (autoclave) in the manufacturing ofsilicone hydrogel contact lenses. Typically, contact lenses, which arehydrated and packaged in a packaging solution, must be sterilized.Sterilization of the hydrated lenses during manufacturing and packagingis typically accomplished by autoclaving. The autoclaving processinvolves heating the packaging of a contact lens to a temperature offrom about 115° C. to about 125° C. for approximately 20-40 minutesunder pressure. The resultant contact lenses not only can have a highsurface hydrophilicity/wettability, no or minimal surface changes, goodintactness, and good durability, but also can be used directly from thelens package by a patient without washing and/or rising because of theophthalmic compatibility of the packaging solution.

The invention, in one aspect, provides a method for producing siliconehydrogel contact lenses each having a crosslinked hydrophilic coatingthereon, the method of invention comprising the steps of: (a) obtaininga silicone hydrogel contact lens; (b) applying a layer ofcarboxyl-containing polymeric material onto the silicone hydrogelcontact lens; (c) placing the silicone hydrogel contact lens with thelayer of carboxyl-containing polymeric material thereon into a lenspackage containing a packaging solution, wherein the packaging solutioncomprises one or more crosslinkable hydrophilic polymeric materialsselected from the group consisting of (i) a water-soluble hydrophilicpolymer polymeric material having epoxide groups, wherein thehydrophilic polymeric material is partial reaction product of a firstmulti-arm polyethyleneglycol having terminal epoxide groups and a firsthydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,hydroxyl group, thiol group, and combination thereof, (ii) a secondmulti-arm polyethyleneglycol having terminal epoxide groups, (iii) amixture of a third multi-arm polyethyleneglycol having terminal epoxidegroups and a second hydrophilicity-enhancing agent having at least onereactive functional group selected from the group consisting of aminogroup, carboxyl group, hydroxyl group, thiol group, and combinationthereof, and (iv) a combination thereof; (d) sealing the package; (e)autoclaving the sealed package with the silicone hydrogel contact lenstherein at a temperature from about 115° C. to about 125° C. for atleast about twenty minutes, thereby forming a non-silicone hydrogelcoating on the silicone hydrogel contact lens, wherein the non-siliconehydrogel coating is a crosslinked polymeric material composed of thecarboxyl-containing polymeric material crosslinked with the one or morecrosslinkable material.

A person skilled in the art knows very well how to make contact lenses.For example, contact lenses can be produced in a conventional“spin-casting mold,” as described for example in U.S. Pat. No.3,408,429, or by the full cast-molding process in a static form, asdescribed in U.S. Pat. Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464;and 5,849,810. In cast-molding, a lens formulation typically isdispensed into molds and cured (i.e., polymerized and/or crosslinked) inmolds for making contact lenses. For production of silicone hydrogelcontact lenses, a lens formulation for cast-molding generally comprisesat least one components selected from the group consisting of asilicone-containing vinylic monomer, a silicone-containing vinylicmacromer, a silicone-containing prepolymer, a hydrophilic vinylicmonomer, a hydrophilic vinylic macromer, a hydrophobic vinylic monomer,and combination thereof, as well known to a person skilled in the art. Asilicone hydrogel contact lens formulation can also comprise othernecessary components known to a person skilled in the art, such as, forexample, a crosslinking agent, a UV-absorbing agent, a visibilitytinting agent (e.g., dyes, pigments, or mixtures thereof), antimicrobialagents (e.g., preferably silver nanoparticles), a bioactive agent,leachable lubricants, leachable tear-stabilizing agents, and mixturesthereof, as known to a person skilled in the art. Molded siliconehydrogel contact lenses then can be subjected to extraction with anextraction solvent to remove unpolymerized components from the moldedlenses and to hydration process, as known by a person skilled in theart. Numerous silicone hydrogel lens formulations have been described innumerous patents and patent applications published by the filing date ofthis application.

A layer of a carboxyl-containing polymeric material can be applied ontoa silicone hydrogel contact lens by contacting the contact lens with asolution of the carboxyl-containing polymeric material. Contacting of acontact lens with a coating solution can occur by dipping it into thecoating solution or by spraying it with the coating solution. Onecontacting process involves solely dipping the contact lens in a bath ofa coating solution for a period of time or alternatively dipping thecontact lens sequentially in a series of bath of coating solutions for afixed shorter time period for each bath. Another contacting processinvolves solely spray a coating solution. However, a number ofalternatives involve various combinations of spraying- and dipping-stepsmay be designed by a person having ordinary skill in the art. Thecontacting time of a contact lens with a coating solution of a reactivepolymer may last up to about 10 minutes, preferably from about 5 toabout 360 seconds, more preferably from about 5 to about 250 seconds,even more preferably from about 5 to about 200 seconds. Examples ofcontacting methods are described in U.S. Pat. Ser. Nos. 6,451,871,6,719,929, 6,793,973, 6,811,805, and 6,896,926 and in U.S. PatentApplication Publication Nos. 2007/0229758A1, 2008/0152800A1, and2008/0226922A1, (herein incorporated by references in their entireties).

In accordance with this embodiment, the carboxyl-containing polymericmaterial can be a linear or branched polymer having pendant carboxylgroups. Any polymers having pendant carboxyl groups can be used informing the layer of the carboxyl-containing material on siliconehydrogel contact lenses. Examples of such carboxyl-containing polymersinclude without limitation: a homopolymer of a carboxyl-containingvinylic monomer (any one as described below); a copolymer of two or morecarboxyl-containing vinylic monomers; a copolymer of acarboxyl-containing vinylic monomer with one or more vinylic monomers,preferably with one or more non-reactive hydrophilic vinylic monomers; acarboxyl-containing cellulose (e.g., carboxymethyl cellulose,carboxyethyl cellulose, carboxypropyl cellulose); poly(glutamic acid);poly(aspartic acid); and combinations thereof.

Examples of carboxyl-containing vinylic monomers include withoutlimitation acrylic acid, a C₁-C₄ alkylacrylic acid (e.g., methacrylicacid, ethylacrylic acid, propylacrylic acid, butylacrylic acid),N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic acid),alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid,angelic acid, cinnamic acid, 1-carobxy-4-phenyl butadiene-1,3, itaconicacid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid,maleic acid, fumaric acid, and combination thereof.

Preferred examples of non-reactive hydrophilic vinylic monomers includewithout limitation acrylamide (AAm), methacrylamideN,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide (DMMA),N-vinylpyrrolidone (NVP), N,N,-dimethylaminoethylmethacrylate (DMAEM),N,N-dimethylaminoethylacrylate (DMAEA),N,N-dimethylaminopropylmethacrylamide (DMAPMAm),N,N-dimethylaminopropylacrylamide (DMAPAAm), glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl(meth)acrylate, hydroxypropyl(meth)acrylate, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide,N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinylalcohol (hydrolyzed form of vinyl acetate in the copolymer), aphosphorylcholine-containing vinylic monomer (including(meth)acryloyloxyethyl phosphorylcholine and those described in U.S.Pat. No. 5,461,433, herein incorporated by reference in its entirety),and combinations thereof.

Preferably, the carboxyl-containing polymeric material used in theinvention is polyacrylic acid, polymethacrylic acid, poly(C₂-C₁₂alkylacrylic acid), poly[acrylic acid-co-methacrylic acid],poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylicacid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone],poly[C₂-C₁₂ alkylacrylic acid-co-acrylamide], poly[C₂-C₁₂ alkylacrylicacid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylicacid-co-vinylacetate], hydrolyzed poly[C₂-C₁₂ alkylacrylicacid-co-vinylacetate], polyethyleneimine (PEI), polyallylaminehydrochloride (PAH) homo- or copolymer, polyvinylamine homo- orcopolymer, or combinations thereof.

The weight average molecular weight M_(w) of a carboxyl-containingpolymeric material used in the invention is at least about 10,000Daltons, preferably at least about 50,000 Daltons, more preferably fromabout 100,000 Daltons to about 5,000,000 Daltons.

A solution of a carboxyl-containing polymeric material can be preparedby dissolving the carboxyl-containing polymeric material in water, amixture of water and one or more organic solvents miscible with water,an organic solvent, or a mixture of one or more organic solvents.Preferably, the carboxyl-containing polymeric material is dissolved in amixture of water and one or more organic solvents, an organic solvent,or a mixture of one or more organic solvent. It is believed that asolvent system containing at least one organic solvent can swell asilicone hydrogel contact lens so that a portion of thecarboxyl-containing polymeric material may penetrate into the siliconehydrogel contact lens and increase the durability of the hydrogelcoating to be formed. Any organic solvents can be used in preparation ofa solution of the carboxyl-containing polymeric material. Examples ofpreferred organic solvents include without limitation tetrahydrofuran,tripropylene glycol methyl ether, dipropylene glycol methyl ether,ethylene glycol n-butyl ether, ketones (e.g., acetone, methyl ethylketone, etc.), diethylene glycol n-butyl ether, diethylene glycol methylether, ethylene glycol phenyl ether, propylene glycol methyl ether,propylene glycol methyl ether acetate, dipropylene glycol methyl etheracetate, propylene glycol n-propyl ether, dipropylene glycol n-propylether, tripropylene glycol n-butyl ether, propylene glycol n-butylether, dipropylene glycol n-butyl ether, tripropylene glycol n-butylether, propylene glycol phenyl ether dipropylene glycol dimetyl ether,polyethylene glycols, polypropylene glycols, ethyl acetate, butylacetate, amyl acetate, methyl lactate, ethyl lactate, i-propyl lactate,methylene chloride, methanol, ethanol, 1- or 2-propanol, 1- or2-butanol, tert-butanol, tert-amyl alcohol, menthol, cyclohexanol,cyclopentanol and exonorborneol, 2-pentanol, 3-pentanol, 2-hexanol,3-hexanol, 3-methyl-2-butanol, 2-heptanol, 2-octanol, 2-nonanol,2-decanol, 3-octanol, norborneol, 2-methyl-2-pentanol,2,3-dimethyl-2-butanol, 3-methyl-3-pentanol, 1-methylcyclohexanol,2-methyl-2-hexanol, 3,7-dimethyl-3-octanol,1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol,2-2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol,3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol,4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol,3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol,4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol,2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol,1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene,4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol,2-methoxy-2-methyl-2-propanol 2,3,4-trimethyl-3-pentanol,3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanoland 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-pyrrolidone,N,N-dimethylpropionamide, dimethyl formamide, dimethyl acetamide,dimethyl propionamide, N-methyl pyrrolidinone, and mixtures thereof.

Lens packages (or containers) are well known to a person skilled in theart for autoclaving and storing a soft contact lens. Any lens packagescan be used in the invention. Preferably, a lens package is a blisterpackage which comprises a base and a cover, wherein the cover isdetachably sealed to the base, wherein the base includes a cavity forreceiving a sterile packaging solution and the contact lens.

Lenses are packaged in individual packages, sealed, and sterilized (byautoclave at about 120° C. or higher for at least about 20 minutes)prior to dispensing to users. A person skilled in the art willunderstand well how to seal and sterilize lens packages.

In accordance with the invention, a packaging solution contains at leastone buffering agent and one or more other ingredients known to a personskilled in the art. Examples of other ingredients include withoutlimitation, tonicity agents, surfactants, antibacterial agents,preservatives, and lubricants (or water-soluble viscosity builders)(e.g., cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).

The packaging solution contains a buffering agent in an amountsufficient to maintain a pH of the packaging solution in the desiredrange, for example, preferably in a physiologically acceptable range ofabout 6 to about 8.5. Any known, physiologically compatible bufferingagents can be used. Suitable buffering agents as a constituent of thecontact lens care composition according to the invention are known tothe person skilled in the art.

The packaging solution has a tonicity of from about 200 to about 450milliosmol (mOsm), preferably from about 250 to about 350 mOsm. Thetonicity of a packaging solution can be adjusted by adding organic orinorganic substances which affect the tonicity. Suitable occularlyacceptable tonicity agents include, but are not limited to sodiumchloride, potassium chloride, glycerol, propylene glycol, polyols,mannitols, sorbitol, xylitol and mixtures thereof.

A packaging solution of the invention has a viscosity of from about 1centipoise to about 7.5 centipoises, preferably from about 1.2centipoises to about 5 centipoises, more preferably from about 1.5centipoises to about 4 centipoises, at 25° C.

In accordance with the invention, the packaging solution comprises oneor more crosslinkable materials selected from the group consisting of(i) a water-soluble hydrophilic polymer polymeric material havingepoxide groups, wherein the hydrophilic polymeric material is partialreaction product of a first multi-arm polyethyleneglycol having terminalepoxide groups and a first hydrophilicity-enhancing agent having atleast one reactive functional group selected from the group consistingof amino group, carboxyl group, hydroxyl group, thiol group, andcombination thereof, (ii) a second multi-arm polyethyleneglycol havingterminal epoxide groups, (iii) a mixture of a third multi-armpolyethyleneglycol having terminal epoxide groups and a secondhydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,hydroxyl group, thiol group, and combination thereof, and (iv) acombination thereof. In a preferred embodiment, the packaging solutioncomprises preferably from about 0.01% to about 2%, more preferably fromabout 0.05% to about 1.5%, even more preferably from about 0.1% to about1%, most preferably from about 0.2% to about 0.5%, by weight of one ormore crosslinkable material.

Any multi-arm polyethylene glycol terminated with epoxide groups can beused in the invention. Various multi-arm polyethylene glycols terminatedwith epoxide groups can be obtained commercial sources, e.g., LaysanBio, Inc. (Arab, Ala., USA), Creative PEGWorks (Winston Salem, N.C.,USA), etc. Alternatively, multi-arm polyethylene glycols terminated withepoxide groups can be obtained from commercially available multi-armpolyethylene glycols with terminal thiol, amino (primary or secondary),carboxyl, or hydroxyl groups. For example, a commercially-availablemulti-arm polyethylene glycol terminated with thiol groups (e.g., fromSigma-Aldrich) can be reacted with glycidyl(meth)acrylate under MichaelAddition reaction to form a multi-arm polyethylene glycols terminatedwith epoxide groups. Further, a commercially-available multi-armpolyethylene glycol terminated with (primary or secondary) amino groups,carboxyl groups or hydroxyl groups (e.g., from Sigma-Aldrich) can bereacted with a 1-chloro-2,3-epoxypropane under known coupling reactionconditions to form a multi-arm polyethylene glycol with terminal epoxidegroups.

In accordance with the invention, a water-soluble hydrophilic polymerpolymeric material having epoxide groups is a partial reaction productof a first multi-arm polyethyleneglycol having terminal epoxide groupsand a first hydrophilicity-enhancing agent having at least one reactivefunctional group selected from the group consisting of amino group,carboxyl group, hydroxyl group, thiol group, and combination thereof.The water-soluble hydrophilic polymer polymeric material having epoxidegroups preferably comprises (i.e., has a composition including) fromabout 20% to about 95%, more preferably from about 35% to about 90%,even more preferably from about 50% to about 85%, by weight of firstpolymer chains derived from a first multi-arm polyethyleneglycol havingterminal epoxide groups and preferably from about 5% to about 80%, morepreferably from about 10% to about 65%, even more preferably from about15% to about 50%, by weight of hydrophilic moieties or second polymerchains derived from at least one hydrophilicity-enhancing agent havingat least one reactive functional group selected from the groupconsisting of amino group, carboxyl group, hydroxyl, thiol group, andcombination thereof. The composition of the hydrophilic polymericmaterial is determined by the composition (based on the total weight ofthe reactants) of a reactants mixture used for preparing thecrosslinkable hydrophilic polymeric material. For example, if a reactantmixture comprises about 75% by weight of a first multi-armpolyethyleneglycol having terminal epoxide groups and about 25% byweight of at least one hydrophilicity-enhancing agent based on the totalweight of the reactants, then the resultant hydrophilic polymericmaterial comprise about 75% by weight of first polymer chains derivedfrom the first multi-arm polyethyleneglycol having terminal epoxidegroups and about 25% by weight of hydrophilic moieties or second polymerchains derived from said at least one hydrophilicity-enhancing agent.The epoxide groups of the crosslinkable hydrophilic polymeric materialare those epoxide groups (of the first multi-arm polyethyleneglycolhaving terminal epoxide groups) which do not participate in crosslinkingreactions for preparing the crosslinkable hydrophilic polymericmaterial.

Any suitable hydrophilicity-enhancing agents can be used in theinvention so long as they contain at least one amino group, at least onecarboxyl group, at least one hydroxyl, and/or at least one thiol group.

A preferred class of hydrophilicity-enhancing agents include withoutlimitation: amino-, carboxyl- or thiol-containing monosaccharides (e.g.,3-amino-1,2-propanediol, 1-thiolglycerol, 5-keto-D-gluconic acid,galactosamine, glucosamine, galacturonic acid, gluconic acid,glucosaminic acid, mannosamine, saccharic acid 1,4-lactone, saccharideacid, Ketodeoxynonulosonic acid, N-methyl-D-glucamine,1-amino-1-deoxy-β-D-galactose, 1-amino-1-deoxysorbitol,1-methylamino-1-deoxysorbitol, N-aminoethyl gluconamide); amino-,carboxyl- or thiol-containing disaccharides (e.g., chondroitindisaccharide sodium salt, di(β-D-xylopyranosyl)amine, digalacturonicacid, heparin disaccharide, hyaluronic acid disaccharide, Lactobionicacid); and amino-, carboxyl- or thiol-containing oligosaccharides (e.g.,carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid); andcombinations thereof.

Another preferred class of hydrophilicity-enhancing agents ishydrophilic polymers having one or more amino, carboxyl and/or thiolgroups. More preferably, the content of monomeric units having an amino(—NHR′ with R′ as defined above), carboxyl (—COOH) and/or thiol (—SH)group in a hydrophilic polymer as a hydrophilicity-enhancing agent isless than about 40%, preferably less than about 30%, more preferablyless than about 20%, even more preferably less than about 10%, by weightbased on the total weight of the hydrophilic polymer.

Another preferred class of hydrophilic polymers ashydrophilicity-enhancing agents are amino- or carboxyl-containingpolysaccharides, for example, such as, carboxymethylcellulose (having acarboxyl content of about 40% or less, which is estimated based on thecomposition of repeating units, —[C₆H_(10-m)O₅(CH₂CO₂H)_(m)]— in which mis 1 to 3), carboxyethylcellulose (having a carboxyl content of about36% or less, which is estimated based on the composition of repeatingunits, —[C₆H_(10-m)O₅(C₂H₄CO₂H)_(m)]— in which m is 1 to 3)carboxypropylcellulose (having a carboxyl content of about 32% or less,which is estimated based on the composition of repeating units,—[C₆H_(10-m)O₅(C₃H₆CO₂H)_(m)]—, in which m is 1 to 3), hyaluronic acid(having a carboxyl content of about 11%, which is estimated based on thecomposition of repeating units, —(C₁₃H20O₉NCO₂H)—), chondroitin sulfate(having a carboxyl content of about 9.8%, which is estimated based onthe composition of repeating units, —(C₁₂H₁₈O₁₃NS CO₂H)—), orcombinations thereof.

Another preferred class of hydrophilic polymers ashydrophilicity-enhancing agents include without limitation:poly(ethylene glycol) (PEG) with one sole amino, carboxyl, thiol, orhydroxyl group (e.g., PEG-NH₂, PEG-SH, PEG-COOH, PEG-OH); H₂N-PEG-NH₂;HOOC-PEG-COOH; HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH; H₂N-PEG-SH;multi-arm PEG with one or more amino, hydroxyl, carboxyl and/or thiolgroups; PEG dendrimers with one or more amino, hydroxyl, carboxyl and/orthiol groups; a diamino- or dicarboxyl-terminated homo- or co-polymer ofa non-reactive hydrophilic vinylic monomer (any one described above); amonoamino- or monocarboxyl-terminated homo- or co-polymer of anon-reactive hydrophilic vinylic monomer (any one described above); acopolymer which is a polymerization product of a composition comprising(1) about 50% by weight or less, preferably from about 0.1% to about30%, more preferably from about 0.5% to about 20%, even more preferablyfrom about 1% to about 15%, by weight of one or more reactive vinylicmonomers (having at least one amino or carboxyl groups) and (2) at leastone non-reactive hydrophilic vinylic monomer (any one described above)and/or at least one phosphorylcholine-containing vinylic monomer; andcombinations thereof.

Examples of preferred reactive vinylic monomers include withoutlimitation amino-C₂-C₆ alkyl(meth)acrylate, C₁-C₆ alkylamino-C₂-C₆alkyl(meth)acrylate, allylamine, vinylamine, amino-C₂-C₆alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl(meth)acrylamide,acrylic acid, C₁-C₄ alkylacrylic acid (e.g., methacrylic ethylacrylicacid, propylacrylic acid, butylacrylic acid), N,N-2-acrylamidoglycolicacid, beta methyl-acrylic acid (crotonic acid), alpha-phenyl acrylicacid, beta-acryloxy propionic acid, sorbic acid, angelic acid, cinnamicacid, 1-carobxy-4-phenyl butadiene-1,3, itaconic acid, citraconic acid,mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaricacid, tricarboxy ethylene, and combinations thereof. Preferably, thereactive vinylic monomer is selected from the group consisting ofamino-C₂-C₆ alkyl(meth)acrylate, C₁-C₆ alkylamino-C₂-C₆alkyl(meth)acrylate, allylamine, vinylamine, amino-C₁-C₆alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl(meth)acrylamide,acrylic acid, C₁-C₆ alkylacrylic acid, N,N-2-acrylamidoglycolic acid,and combinations thereof.

In a more preferred embodiment, a hydrophilic polymer as ahydrophilicity-enhancing agent is PEG-NH₂; PEG-SH; PEG-COOH;H₂N-PEG-NH₂; HOOC-PEG-COOH; HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH;H₂N-PEG-SH; multi-arm PEG with one or more amino, carboxyl or thiolgroups; PEG dendrimers with one or more amino, carboxyl or thiol groups;a monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- orcopolymer of a non-reactive hydrophilic vinylic monomer selected fromthe group consisting of acryamide (AAm), N,N-dimethylacrylamide (DMA),N-vinylpyrrolidone (NVP), N-vinyl-N-methyl acetamide,glycerol(meth)acrylate, hydroxyethyl(meth)acrylate,N-hydroxyethyl(meth)acrylamide, C₁-C₄-alkoxy polyethyleneglycol(meth)acrylate having a weight average molecular weight of up to400 Daltons, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone,N,N-dimethylaminoethyl(meth)acrylate,N,N-dimethylaminopropyl(metha)crylamide, (meth)acryloyloxyethylphosphorylcholine, and combinations thereof; a copolymer which is apolymerization product of a composition comprising (1) from about 0.1%to about 30%, preferably from about 0.5% to about 20%, more preferablyfrom about 1% to about 15%, by weight of (meth)acrylic acid, C₂-C₁₂alkylacrylic acid, vinylamine, allylamine and/or amino-C₂-C₄alkyl(meth)acrylate, and (2) (meth)acryloyloxyethyl phosphorylcholineand/or at least one non-reactive hydrophilic vinylic monomer selectedfrom the group consisting of acryamide, N,N-dimethylacrylamide,N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, glycerol(meth)acrylate,hydroxyethyl(meth)acrylate, N-hydroxyethyl(meth)acrylamide, C₁-C₄-alkoxypolyethylene glycol(meth)acrylate having a weight average molecularweight of up to 400 Daltons, vinyl alcohol, and combination thereof.

Most preferably, the hydrophilicity-enhancing agent is PEG-N H₂; PEG-SH;PEG-COOH; monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpolyvinylpyrrolidone; monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated polyacrylamide; monoamino-, monocarboxyl-,diamino- or dicarboxyl-terminated poly(DMA); monoamino- ormonocarboxyl-, diamino- or dicarboxyl-terminated poly(DMA-co-NVP);monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpoly(NVP-co-N,N-dimethylaminoethyl(meth)acrylate)); monoamino-,monocarboxyl-, diamino- or dicarboxyl-terminated poly(vinylalcohol);monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpoly[(meth)acryloyloxyethyl phosphrylcholine] homopolymer or copolymer;monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpoly(NVP-co-vinyl alcohol); monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated poly(DMA-co-vinyl alcohol); poly[(meth)acrylicacid-co-acrylamide] with from about 0.1% to about 30%, preferably fromabout 0.5% to about 20%, more preferably from about 1% to about 15%, byweight of (meth)acrylic acid; poly[(meth)acrylic acid-co-NVP) with fromabout 0.1% to about 30%, preferably from about 0.5% to about 20%, morepreferably from about 1% to about 15%, by weight of (meth)acrylic acid;a copolymer which is a polymerization product of a compositioncomprising (1) (meth)acryloyloxyethyl phosphorylcholine and (2) fromabout 0.1% to about 30%, preferably from about 0.5% to about 20%, morepreferably from about 1% to about 15%, by weight of a carboxylic acidcontaining vinylic monomer and/or an amino-containing vinylic monomer;and combination thereof.

PEGs with functional groups and multi-arm PEGs with functional groupscan be obtained from various commercial suppliers, e.g., Sigma-Aldrich,Polyscience, and Shearwater Polymers, inc., etc.

Monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- orcopolymers of one or more non-reactive hydrophilic vinylic monomers orof a phosphorylcholine-containing vinylic monomer can be preparedaccording to procedures described in U.S. Pat. No. 6,218,508, hereinincorporated by reference in its entirety. For example, to prepare adiamino- or dicarboxyl-terminated homo- or co-polymer of a non-reactivehydrophilic vinylic monomer, the non-reactive vinylic monomer, a chaintransfer agent with an amino or carboxyl group (e.g.,2-aminoethanethiol, 2-mercaptopropinic acid, thioglycolic acid,thiolactic acid, or other hydroxymercaptanes, aminomercaptans, orcarboxyl-containing mercaptanes) and optionally other vinylic monomerare copolymerized (thermally or actinically) with a reactive vinylicmonomer (having an amino or carboxyl group), in the presence of anfree-radical initiator. Generally, the molar ratio of chain transferagent to that of all of vinylic monomers other than the reactive vinylicmonomer is from about 1:5 to about 1:100, whereas the molar ratio ofchain transfer agent to the reactive vinylic monomer is 1:1. In suchpreparation, the chain transfer agent with amino or carboxyl group isused to control the molecular weight of the resultant hydrophilicpolymer and forms a terminal end of the resultant hydrophilic polymer soas to provide the resultant hydrophilic polymer with one terminal aminoor carboxyl group, while the reactive vinylic monomer provides the otherterminal carboxyl or amino group to the resultant hydrophilic polymer.Similarly, to prepare a monoamino- or monocarboxyl-terminated homo- orco-polymer of a non-reactive hydrophilic vinylic monomer, thenon-reactive vinylic monomer, a chain transfer agent with an amino orcarboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropinic acid,thioglycolic acid, thiolactic acid, or other hydroxymercaptanes,aminomercaptans, or carboxyl-containing mercaptanes) and optionallyother vinylic monomers are copolymerized (thermally or actinically) inthe absence of any reactive vinylic monomer.

As used herein, a copolymer of a non-reactive hydrophilic vinylicmonomer refers to a polymerization product of a non-reactive hydrophilicvinylic monomer with one or more additional vinylic monomers. Copolymerscomprising a non-reactive hydrophilic vinylic monomer and a reactivevinylic monomer (e.g., a carboxyl-containing vinylic monomer) can beprepared according to any well-known radical polymerization methods orobtained from commercial suppliers. Copolymers containingmethacryloyloxyethyl phosphorylcholine and carboxyl-containing vinylicmonomer can be obtained from NOP Corporation (e.g., LIPIDURE®-A and-AF).

The weight average molecular weight M_(w) of the hydrophilic polymerhaving at least one amino, carboxyl or thiol group (as ahydrophilicity-enhancing agent) is preferably from about 500 to about1,000,000, more preferably from about 1,000 to about 500,000.

In accordance with the invention, the reaction between ahydrophilicity-enhancing agent and a multi-arm polyethylene glycol withterminal epoxide groups is carried out at a temperature of from about40° C. to about 80° C. for a period of time sufficient (from about 0.3hour to about 24 hours, preferably from about 1 hour to about 12 hours,even more preferably from about 2 hours to about 8 hours) to form awater-soluble crosslinkable hydrophilic polymeric material containingepoxide groups.

In accordance with the invention, the concentration of ahydrophilicity-enhancing agent relative to a multi-arm polyethyleneglycol with terminal epoxide groups must be selected not to render aresultant hydrophilic polymeric material water-insoluble (i.e., asolubility of less than 0.005 g per 100 ml of water at room temperature)and not to consume more than about 99%, preferably about 98%, morepreferably about 97%, even more preferably about 96% of the epoxidegroups of the epichlorohydrin-functionalized polyamine orpolyamidoamine.

The packaging solution preferably comprises an α-oxo-multi-acid or saltthereof in an amount sufficient to have a reduced susceptibility tooxidation degradation of the polyethylene glycol segments. Acommonly-owned co-pending patent application (US patent applicationpublication No. 2004/0116564 A1, incorporated herein in its entirety)discloses that oxo-multi-acid or salt thereof can reduce thesusceptibility to oxidative degradation of a PEG-containing polymericmaterial.

Exemplary α-oxo-multi-acids or biocompatible salts thereof includewithout limitation citric acid, 2-ketoglutaric acid, or malic acid orbiocompatible (preferably ophthalmically compatible) salts thereof. Morepreferably, an α-oxo-multi-acid is citric or malic acid or biocompatible(preferably ophthalmically compatible) salts thereof (e.g., sodium,potassium, or the like).

In accordance with the invention, the packaging solution can furthercomprises mucin-like materials, phospholipids, ophthalmically beneficialmaterials, and/or surfactants.

Exemplary mucin-like materials include without limitation polyglycolicacid, polylactides, and the likes. A mucin-like material can be used asguest materials which can be released continuously and slowly overextended period of time to the ocular surface of the eye for treatingdry eye syndrome. The mucin-like material preferably is present ineffective amounts.

Exemplary ophthalmically beneficial materials include without limitation2-pyrrolidone-5-carboxylic acid (PCA), amino acids (e.g., taurine,glycine, etc.), alpha hydroxyl acids (e.g., glycolic, lactic, malic,tartaric, mandelic and citric acids and salts thereof, etc.), linoleicand gamma linoleic acids, and vitamins (e.g., B5, A, B6, etc.).

Surfactants can be virtually any ocularly acceptable surfactantincluding non-ionic, anionic, and amphoteric surfactants. Examples ofpreferred surfactants include without limitation poloxamers (e.g.,Pluronic® F108, F88, F68, F68LF, F127, F87, F77, P85, P75, P104, andP84), poloamines (e.g., Tetronic® 707, 1107 and 1307, polyethyleneglycol esters of fatty acids (e.g., Tween® 20, Tween® 80),polyoxyethylene or polyoxypropylene ethers of C₁₂-C₁₈ alkanes (e.g.,Brij® 35), polyoxyethyene stearate (Myrj® 52), polyoxyethylene propyleneglycol stearate (Atlas® G 2612), and amphoteric surfactants under thetrade names Mirataine® and Miranol®.

A person skilled in the art knows well how to perform the autoclavingprocess involved in the invention. In accordance with this embodiment ofthe invention, the packaging solution is a buffered aqueous solutionwhich is ophthalmically safe after autoclave.

A silicone hydrogel contact lens obtained according a method of theinvention has at least one of the properties selected from the groupconsisting of: an oxygen permeability of at least about 40 barrers,preferably at least about 50 barrers, more preferably at least about 60barrers, even more preferably at least about 70 barrers; an elasticmodulus of about 1.5 MPa or less, preferably about 1.2 MPa or less, morepreferably about 1.0 or less, even more preferably from about 0.3 MPa toabout 1.0 MPa; an lonoflux Diffusion Coefficient, D, of, preferably atleast about 1.5×10⁻⁶ mm²/min, more preferably at least about 2.6×10⁻⁶mm²/min, even more preferably at least about 6.4×10⁻⁶ mm²/min; a watercontent of preferably from about 18% to about 70%, more preferably fromabout 20% to about 60% by weight when fully hydrated; or combinationsthereof.

It should be understood that although various embodiments includingpreferred embodiments of the invention may be separately describedabove, they can be combined and/or used together in any desirablefashion in the method of the invention for producing silicone hydrogelcontact lenses each having a crosslinked hydrophilic coating thereon.

In another aspect, the invention provides a silicone hydrogel contactlens obtained according to a method of invention described above.

The previous disclosure will enable one having ordinary skill in the artto practice the invention. Various modifications, variations, andcombinations can be made to the various embodiment described herein. Inorder to better enable the reader to understand specific embodiments andthe advantages thereof, reference to the following examples issuggested. It is intended that the specification and examples beconsidered as exemplary.

Although various embodiments of the invention have been described usingspecific terms, devices, and methods, such description is forillustrative purposes only. The words used are words of descriptionrather than of limitation. It is to be understood that changes andvariations may be made by those skilled in the art without departingfrom the spirit or scope of the present invention, which is set forth inthe following claims. In addition, it should be understood that aspectsof the various embodiments may be interchanged either in whole or inpart or can be combined in any manner and/or used together. Therefore,the spirit and scope of the appended claims should not be limited to thedescription of the preferred versions contained therein.

EXAMPLE 1

Oxygen Permeability Measurements

The apparent oxygen permeability of a lens and oxygen transmissibilityof a lens material is determined according to a technique similar to theone described in U.S. Pat. No. 5,760,100 and in an article by Wintertonet al., (The Cornea: Transactions of the World Congress on the Cornea111, H. D. Cavanagh Ed., Raven Press: New York 1988, pp 273-280), bothof which are herein incorporated by reference in their entireties.Oxygen fluxes (J) are measured at 34° C. in a wet cell (i.e., gasstreams are maintained at about 100% relative humidity) using a Dk1000instrument (available from Applied Design and Development Co., Norcross,Ga.), or similar analytical instrument. An air stream, having a knownpercentage of oxygen (e.g., 21%), is passed across one side of the lensat a rate of about 10 to 20 cm³/min., while a nitrogen stream is passedon the opposite side of the lens at a rate of about 10 to 20 cm³/min. Asample is equilibrated in a test media (i.e., saline or distilled water)at the prescribed test temperature for at least 30 minutes prior tomeasurement but not more than 45 minutes. Any test media used as theoverlayer is equilibrated at the prescribed test temperature for atleast 30 minutes prior to measurement but not more than 45 minutes. Thestir motor's speed is set to 1200±50 rpm, corresponding to an indicatedsetting of 400±15 on the stepper motor controller. The barometricpressure surrounding the system, P_(measured), is measured. Thethickness (t) of the lens in the area being exposed for testing isdetermined by measuring about 10 locations with a Mitotoya micrometerVL-50, or similar instrument, and averaging the measurements. The oxygenconcentration in the nitrogen stream (i.e., oxygen which diffusesthrough the lens) is measured using the DK1000 instrument. The apparentoxygen permeability of the lens material, Dk_(app), is determined fromthe following formula:Dk_(app)=Jt/P_(oxygen))where J=oxygen flux [microliters O₂ /cm²-minute]

P_(oxygen)=(P_(measured)−P_(water) vapor)=(% O₂ in air stream) [mmHg]=partial pressure of oxygen in the air stream

P_(measured)=barometric pressure (mm Hg)

P_(water) vapor=0 mm Hg at 34° C. (in a dry cell) (mm Hg)

P_(water) vapor=40 mm Hg at 34° C. (in a wet cell) (mm Hg)

t=average thickness of the lens over the exposed test area (mm)

Dk_(app) is expressed in units of barrers.

The apparent oxygen transmissibility (Dk/t) of the material may becalculated by dividing the apparent oxygen permeability (Dk_(app)) bythe average thickness (t) of the lens.

The above described measurements are not corrected for the so-calledboundary layer effect which is attributable to the use of a water orsaline bath on top of the contact lens during the oxygen fluxmeasurement. The boundary layer effect causes the reported value for theapparent Dk of a silicone hydrogel material to be lower than the actualintrinsic Dk value. Further, the relative impact of the boundary layereffect is greater for thinner lenses than with thicker lenses. The neteffect is that the reported Dk appear to change as a function of lensthickness when it should remain constant.

The intrinsic Dk value of a lens can be estimated based on a Dk valuecorrected for the surface resistance to oxygen flux caused by theboundary layer effect as follows.

Measure the apparent oxygen permeability values (single point) of thereference lotrafilcon A (Focus® N&D® from CIBA VISION CORPORATION) orlotrafilcon B (AirOptix™ from CIBA VISION CORPORATION) lenses using thesame equipment. The reference lenses are of similar optical power as thetest lenses and are measured concurrently with the test lenses.

Measure the oxygen flux through a thickness series of lotrafilcon A orlotrafilcon B (reference) lenses using the same equipment according tothe procedure for apparent Dk measurements described above, to obtainthe intrinsic Dk value (Dk_(i)) of the reference lens. A thicknessseries should cover a thickness range of approximately 100 μm or more.Preferably, the range of reference lens thicknesses will bracket thetest lens thicknesses. The Dk_(app) of these reference lenses must bemeasured on the same equipment as the test lenses and should ideally bemeasured contemporaneously with the test lenses. The equipment setup andmeasurement parameters should be held constant throughout theexperiment. The individual samples may be measured multiple times ifdesired.

Determine the residual oxygen resistance value, R_(r), from thereference lens results using equation 1 in the calculations.

$\begin{matrix}{R_{r} = \frac{\sum\left( {\frac{t}{{Dk}_{app}} - \frac{t}{{Dk}_{i}}} \right)}{n}} & (1)\end{matrix}$In which t is the thickness of the test lens (i.e., the reference lenstoo), and n is the number of the reference lenses measured. Plot theresidual oxygen resistance value, R_(r) vs. t data and fit a curve ofthe form Y=a+bX where, for the jth lens, Y_(j)=(ΔP/J)_(j) and X=t_(j).The residual oxygen resistance, R_(r) is equal to a.

Use the residual oxygen resistance value determined above to calculatethe correct oxygen permeability Dk_(c) (estimated intrinsic Dk) for thetest lenses based on Equation 2.Dk _(c) =t/[(t/Dk _(a))−R_(r)]  (2)

The estimated intrinsic Dk of the test lens can be used to calculatewhat the apparent Dk (Dk_(a) _(_) _(std)) would have been for a standardthickness lens in the same test environment based on Equation 3. Thestandard thickness (t_(std)) for lotrafilcon A=85 μm. The standardthickness for lotrafilcon B=60 μm.Dk _(a) _(_) _(std) =t _(std)/[(t _(std) /Dk _(c))+R_(r) _(_)_(std)]  (3)Ion Permeability Measurements.

The ion permeability of a lens is measured according to proceduresdescribed in U.S. Pat. No. 5,760,100 (herein incorporated by referencein its entirety. The values of ion permeability reported in thefollowing examples are relative ionoflux diffusion coefficients(D/D_(ref)) in reference to a lens material, Alsacon, as referencematerial. Alsacon has an ionoflux diffusion coefficient of 0.314×10⁻³mm²/minute.

Lubricity Evaluation

The lubricity rating is a qualitative ranking scheme where a scale of 0to 4 is used with 0 or lower numbers indicating better lubricity. 1 isassigned to Oasys™/TruEye™ commercial lenses and 4 is assigned tocommercial Air Optix™ lenses. The samples are rinsed with excess DIwater for at least 3 times and then transferred to PBS before theevaluation. Before the evaluation, hands are rinsed with a soapsolution, extensively rinsed with DI water and then dried with KimWipetowels. The samples are handled between the fingers and a numericalnumber is assigned for each sample relative to the above standardlenses. For consistency, all the ratings are independently collected bythe same two operators in order to avoid bias and all the data so farreveal very good agreement and consistency in the evaluation.

Surface hydrophilicity/wetability Tests. Water contact angle on acontact lens is a general measure of the surface hydrophilicity (orwetability) of the contact lens. In particular, a low water contactangle corresponds to more hydrophilic surface. Average contact angles(Sessile Drop) of contact lenses are measured using a VCA 2500 XEcontact angle measurement device from AST, Inc., located in Boston,Mass. This equipment is capable of measuring advancing or recedingcontact angles or sessile (static) contact angles. The measurements areperformed on fully hydrated contact lenses and immediately afterblot-drying as follows. A contact lens is removed from the vial andwashed 3 times in ˜200 ml of fresh DI water in order to remove looselybound packaging additives from the lens surface. The lens is then placedon top of a lint-free clean cloth (Alpha Wipe TX1009), dabbed well toremove surface water, mounted on the contact angle measurement pedestal,blown dry with a blast of dry air and finally the sessile drop contactangle is automatically measured using the software provided by themanufacturer. The DI water used for measuring the contact angle has aresistivity >18MΩcm and the droplet volume used is 2 μl. Typically,uncoated silicone hydrogel lenses (after autoclave) have a sessile dropcontact angle around 120 degrees. The tweezers and the pedestal arewashed well with Isopropanol and rinsed with DI water before coming incontact with the contact lenses.

Water Break-up Time (WBUT) Tests. The wettabilty of the lenses (afterautoclave) is also assessed by determining the time required for thewater film to start breaking on the lens surface. Briefly, lenses areremoved from the vial and washed 3 times in ˜200 ml of fresh DI water inorder to remove loosely bound packaging additives from the lens surface.The lens is removed from the solution and held against a bright lightsource. The time that is needed for the water film to break (de-wet)exposing the underlying lens material is noted visually. Uncoated lensestypically instantly break upon removal from DI water and are assigned aWBUT of 0 seconds. Lenses exhibiting WBUT ≧5 seconds are consideredwettable and are expected to exhibit adequate wettability (ability tosupport the tear film) on-eye.

Debris Adhesion Test. Contact lens with highly charged surface can besusceptible to increased debris adhesion during patient handling. Apaper towel (e.g., Tork) is rubbed against gloved hands and then bothsides of the lens are rubbed with the fingers to transfer any debris tothe lens surface. The lens is briefly rinsed and then observed under amicroscope. A qualitative rating scale from 0 (no debris adhesion) to 4(debris adhesion equivalent to a polyacrylic acid (PAA) coated controllens) is used to rate each lens. Lenses with a score of “0” or “1” aredeemed to be acceptable.

Coating Intactness Tests. The intactness of a coating on the surface ofa contact lens can be tested according to Sudan Black stain test asfollow. Contact lenses with a coating (an LbL coating, a plasma coating,or any other coatings) are dipped into a Sudan Black dye solution (SudanBlack in vitamin E oil). Sudan Black dye is hydrophobic and has a greattendency to be adsorbed by a hydrophobic material or onto a hydrophobiclens surface or hydrophobic spots on a partially coated surface of ahydrophobic lens (e.g., silicone hydrogel contact lens). If the coatingon a hydrophobic lens is intact, no staining spots should be observed onor in the lens. All of the lenses under test are fully hydrated.

Tests of coating durability. The lenses are digitally rubbed withSolo-care® multi-purpose lens care solution for 30 times and then rinsedwith saline. The above procedure is repeated for a given times, e.g.,from 1 to 30 times, (i.e., number of consecutive digital rubbing testswhich imitate cleaning and soaking cycles). The lenses are thensubjected to Sudan Black test (i.e., coating intactness test describedabove) to examine whether the coating is still intact. To survivedigital rubbing test, there is no significantly increased staining spots(e.g., staining spots covering no more than about 5% of the total lenssurface). Water contact angles are measured to determine the coatingdurability.

Surface Cracking Test. Excessive crosslinking of a coating layer canlead to surface cracks after rubbing a lens which are visible under adarkfield microscope. Lenses are inverted and rubbed and any crackinglines are noted. A qualitative rating of 0 (no cracking) to 2 (severecracking) is used to rate the lenses. Any severe cracking lines aredeemed unacceptable.

EXAMPLE 2

Preparation of Chain-Extended Polydimethylsiloxane Vinylic Macromer withTerminal Methacrylate Groups (CE-PDMS Macromer)

In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane(Mn=2000, Shin-Etsu, KF-6001a) is capped with isophorone diisocyanate(IPDI) by reacting 49.85 g ofα,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g IPDI in150 g of dry methyl ethyl ketone (MEK) in the presence of 0.063 g ofdibutyltindilaurate (DBTDL). The reaction is kept for 4.5 h at 40° C.,forming IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g ofa,w-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=3000, Shin-Etsu,KF-6002) and 50 g of dry MEK are added dropwise to the IPDI-PDMS-IPDIsolution to which has been added an additional 0.063 g of DBTDL. Thereactor is held for 4.5 h at about 40° C., formingHO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. MEK is then removed under reducedpressure. In the third step, the terminal hydroxyl-groups are cappedwith methacryloyloxyethyl groups in a third step by addition of 7.77 gof isocyanatoethylmethacrylate (IEM) and an additional 0.063 g of DBTDL,forming IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM.

Alternate Preparation of CE-PDMS Macromer with Terminal MethacrylateGroups

240.43 g of KF-6001 is added into a 1-L reactor equipped with stirring,thermometer, cryostat, dropping funnel, and nitrogen/vacuum inletadapter, and then dried by application of high vacuum (2×10⁻² mBar).Then, under an atmosphere of dry nitrogen, 320 g of distilled MEK isthen added into the reactor and the mixture is stirred thoroughly. 0.235g of DBTDL is added to the reactor. After the reactor is warmed to 45°C., 45.86 g of IPDI are added through an addition funnel over 10 minutesto the reactor under moderate stirring. The reaction is kept for 2 hoursat 60° C. 630 g of KF-6002 dissolved in 452 g of distilled MEK are thenadded and stirred until a homogeneous solution is formed. 0.235 g ofDBTDL are added, and the reactor is held at about 55° C. overnight undera blanket of dry nitrogen. The next day, MEK is removed by flashdistillation. The reactor is cooled and 22.7 g of IEM are then chargedto the reactor followed by about 0.235 g of DBTDL. After about 3 hours,an additional 3.3 g of IEM are added and the reaction is allowed toproceed overnight. The following day, the reaction mixture is cooled toabout 18° C. to obtain CE-PDMS macromer with terminal methacrylategroups.

EXAMPLE 3

Preparation of Lens Formulations

A lens formulation is prepared by dissolving components in 1-propanol tohave the following composition: 33% by weight of CE-PDMS macromerprepared in Example 2, 17% by weight ofN-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24% by weightof N,N-dimethylacrylamide (DMA), 0.5% by weight ofN-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-disteaoyl-sn-glycero-3-phosphoethanolamin, sodium salt)(L-PEG), 1.0% by weight Darocur 1173 (DC1173), 0.1% by weight ofvisitint (5% copper phthalocyanine blue pigment dispersion intris(trimethylsiloxy)silylpropylmethacrylate, TRIS), and 24.5% by weightof 1-propanol.

Preparation of Lenses

Lenses are prepared by cast-molding from the lens formulation preparedabove in a reusable mold, similar to the mold shown in FIGS. 1-6 in U.S.Pat. Nos. 7,384,590 and 7,387,759 (FIGS. 1-6). The mold comprises afemale mold half made of quartz (or CaF₂) and a male mold half made ofglass (or PMMA). The UV irradiation source is a Hamamatsu lamp with theWG335+TM297 cut off filter at an intensity of about 4 mW/cm². The lensformulation in the mold is irradiated with UV irradiation for about 25seconds. Cast-molded lenses are extracted with isopropanol (or methylethyl ketone, MEK), rinsed in water, coated with polyacrylic acid (PAA)by dipping lenses in a propanol solution of PAA (0.0036% by weight,acidified with formic acid to about pH 2.0), and hydrated in water.Resultant lenses having a reactive PAA-LbL base coating thereon aredetermined to have the following properties: ion permeability of about8.0 to about 9.0 relative to Alsacon lens material; apparent Dk (singlepoint) of about 90 to 100; a water content of about 30% to about 33%;and an elastic modulus of about 0.60 MPa to about 0.65 MPa.

EXAMPLE 4

4-arm PEG epoxide (Mw 10,000) is purchased from Laysan Bio, Inc. andused as received. Phosphate buffered saline (PBS) containing NaCl (0.75%by weight), NaH₂PO₄.H₂O (0.0536% by weight), Na₂HPO₄.2H₂O (0.3576% byweight) and DI water (97.59% by weight) is prepared.

An IPC saline is prepared by adding 1% of 4-arm polyethylene glycolepoxides (4-arm PEG-epoxide) to the PBS prepared above and adjusting thepH to 7.2˜7.4.

Silicon hydrogel lenses prepared in Example 3 are extracted and coatedby dipping in the following series of baths: 3 MEK baths (22, 78 and 224seconds), 1 DI water rinse bath (56 seconds), 2 baths of PAA coatingsolution which is prepared by dissolving 0.036 gm of PAA (Mw: 450kDa,from Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid, for 44and 56 seconds separately; and 3 DI water baths each for 56 seconds.

Lenses having a PAA-LbL coating as described above are placed in apolypropylene shell with 0.55 ml of the IPC saline (half of the salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming acrosslinked (or hydrogel) coating on the lenses.

The resultant lenses pass debris adhesion test according to theprocedures described in Example 1. The lenses have a WBUT of longer than10 seconds. The lenses are very lubricious based on qualitative fingerrubbing tests (lubricity rating of 1).

EXAMPLE 5

Epoxide PEG epoxide (Mw 10,000) is purchased from Laysan Bio and used asreceived. PBS containing NaCl (0.75% by weight), NaH₂PO₄.H₂O (0.0536% byweight), Na₂HPO₄.2H₂O (0.3576% by weight) and DI water (97.59% byweight) is prepared. An IPC saline is prepared by adding 0.1% ofEpoxides-PEG-epoxide) to the prepared PBS and adjusting the pH to7.2˜7.4.

Lenses having a PAA-LbL coating as described in Example 4 are placed ina polypropylene shell with 0.55 ml of the IPC saline (half of the salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming acrosslinked (or hydrogel) coating on the lenses.

The resultant lenses pass debris adhesion test. The lenses have a WBUTof longer than 10 seconds. The lenses are very lubricious based onqualitative finger rubbing tests (lubricity rating of 1).

EXAMPLE 6

Polyethylene imine branched (PEIB, Mw 25000) is purchased from Aldrichand used as received. An IPC saline is prepared by adding 5% of 4-armpolyethylene glycol epoxides (4-arm PEG-epoxide) and 0.001% PEIB to thephosphate buffered saline (PBS) and adjusting the pH to 7.2˜7.4.

Lenses having a PAA-LbL coating as described in Example 4 are placed ina polypropylene shell with 0.55 ml of the IPC saline (half of the salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming acrosslinked (hydrogel) coating on the contact lens.

The resultant lenses pass debris adhesion test. The lenses have a WBUTof 6 seconds. The lenses are very lubricious based on qualitative fingerrubbing tests (lubricity rating of 1).

EXAMPLE 7

Starch (starch from potatoes) purchased from Sigma Aldrich and used asreceived. An IPC solution is prepared by adding 5 wt % 4-armpolyethylene glycol epoxides (4-arm PEG-epoxide) along with 0.1wt % ofstarch to phosphate buffered saline (PBS prepared as described inExample 4). The final pH is adjusted to 11.5. The solution is then heattreated at 40° C. for 3 hours. After the heat treatment, the pH of thesolution is adjusted to 7.2˜7.4 and then filtered using a 0.22 micronpolyether sulphone (PES) membrane filter.

Lenses having a PAA-LbL coating as described in Example 4 are placed ina polypropylene shell with 0.55 ml of the IPC saline (half of the salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming acovalently bonded coating (PAA-x-hydrophilic polymeric material) on thelenses.

The resultant lenses pass debris adhesion test (rating of 1). The lenseshave a WBUT of 10 seconds. The lenses are more lubricious than AirOptix™ lenses based on qualitative finger rubbing tests (lubricityrating of 2).

EXAMPLE 8

Dextran (Mw. 188000) was purchased from Sigma Aldrich and used asreceived. An IPC solution is prepared by adding 5wt % 4- armpolyethylene glycol epoxides (4-arm PEG-epoxide) along with 0.5wt % ofDextran to phosphate buffered saline (PBS prepared as described inExample 4). The final pH is adjusted to 11.5. The solution is then heattreated at 40° C. for 3 hours. After the heat treatment, the pH of thesolution is adjusted to 7.2˜7.4 and then filtered using a 0.22 micronpolyether sulphone (PES) membrane filter.

Lenses having a PAA-LbL coating as described in Example 4 are placed ina polypropylene shell with 0.55 ml of the IPC saline (half of the salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming acrosslinked (or hydrogel) coating on the lenses.

The resultant lenses pass debris adhesion test (rating of 0). The lenseshave a WBUT of longer than 10 seconds. The lenses are more lubriciousthan Air Optix™ lenses based on qualitative finger rubbing tests(lubricity rating of 3).

EXAMPLE 9

Aquacat PF618 is a commercially available 10% aqueous solution ofCationic Guar Gum manufactured by Aqualon division of Hercules, Inc. AnIPC solution is prepared by adding 1wt % 4-arm polyethylene glycolepoxides (4-arm PEG-epoxide) along with 0.01wt % of Aquacat PF618 tophosphate buffered saline (PBS prepared as described in Example 4). Thefinal pH is adjusted to 11.5. The solution is then heat treated at 40°C. for 3 hours. After the heat treatment, the pH of the solution isadjusted to 7.2˜7.4 and then filtered using a 0.22 micron polyethersulphone (PES) membrane filter.

Lenses having a PAA-LbL coating as described in Example 4 are placed ina polypropylene shell with 0.55 ml of the IPC saline (half of the salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming acrosslinked (or hydrogel) coating on the lenses.

The test lenses pass debris adhesion test (rating of 1). The lenses havea WBUT of longer than 10 seconds. The lenses are extremely lubriciousbased on qualitative finger rubbing tests (lubricity rating of 0).

EXAMPLE 10

Kollicoat® (Polyvinyl alcohol-polyethylene glycol graft-copolymer) ispurchased from Sigma Life sciences and used as received. An IPC salineis prepared by adding 5% of 4-arm polyethylene glycol epoxides (4-armPEG-epoxide) and 0.05% Kollicoat to the phosphate buffered saline (PBS)and adjusting the pH to 7.2˜7.4.

Lenses having a PAA-LbL coating as described in Example 4 are placed ina polypropylene shell with 0.55 ml of the IPC saline (half of the salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming acrosslinked coating on the lenses.

The resultant lenses pass debris adhesion test (rating of 0). The lenseshave a WBUT of 7 seconds. The lenses are more lubricious than Air Optix™lenses based on qualitative finger rubbing tests (lubricity rating of3).

EXAMPLE 11

Methoxy-poly(ethylene glycol)-thiol, avg Mw2000 (product# mPEG-SH-2000,Laysan Bio Inc.) is purchased and used as received. An IPC saline isprepared by adding 5% of 4-arm polyethylene glycol epoxides (4-armPEG-epoxide) and 1 wt % of mPEG-SH to the phosphate buffered saline(PBS) and adjusting the pH to 7.2˜7.4.

Lenses having a PAA-LbL coating as described in Example 4 are placed ina polypropylene shell with 0.55 ml of the IPC saline (half of the salineis added prior to inserting the lens). The blister is then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming acrosslinked (or hydrogel) coating on the lenses.

The resultant lenses shows improved resistance to debris adhesion(rating of 2) compared to a PAA-coated lens as control (rating of 4).The lenses have a WBUT of 7 seconds. The lenses are very lubriciousbased on qualitative finger rubbing tests (lubricity rating of 1).

What is claimed is:
 1. A method for producing silicone hydrogel contactlenses each having a crosslinked hydrophilic coating thereon, comprisingthe steps of: (a) obtaining a silicone hydrogel contact lens; (b)applying a layer of carboxyl-containing polymeric material onto thesilicone hydrogel contact lens; (c) placing the silicone hydrogelcontact lens with the layer of carboxyl-containing polymeric materialthereon into a lens package containing a packaging solution, wherein thepackaging solution comprises from about 0.01% to about 2% by weight ofone or more crosslinkable hydrophilic polymeric materials selected fromthe group consisting of (i) a water-soluble hydrophilic polymerpolymeric material having epoxide groups, wherein the hydrophilicpolymeric material is partial reaction product of a first multi-armpolyethyleneglycol having terminal epoxide groups and a firsthydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,hydroxyl group, thiol group, and combination thereof, (ii) a secondmulti-arm polyethyleneglycol having terminal epoxide groups, (iii) amixture of a third multi-arm polyethyleneglycol having terminal epoxidegroups and a second hydrophilicity-enhancing agent having at least onereactive functional group selected from the group consisting of aminogroup, carboxyl group, hydroxyl group, thiol group, and combinationthereof, and (iv) a combination thereof; (d) sealing the package; (e)autoclaving the sealed package with the silicone hydrogel contact lenstherein at a temperature from about 115° C. to about 125° C. for atleast about twenty minutes, thereby forming a non-silicone hydrogelcoating on the silicone hydrogel contact lens, wherein the non-siliconehydrogel coating is a crosslinked polymeric material composed of thecarboxyl-containing polymeric material crosslinked with the one or morecrosslinkable material.
 2. The method of claim 1, wherein the packagingsolution comprises from about 0.05% to about 1.5% by weight of said oneor more crosslinkable materials.
 3. The method of claim 2, wherein thepackaging solution comprises the water-soluble hydrophilic polymerpolymeric material having epoxide groups, wherein the hydrophilicpolymeric material is partial reaction product of a first multi-armpolyethyleneglycol having terminal epoxide groups and a firsthydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,hydroxyl group, thiol group, and combination thereof.
 4. The method ofclaim 3, wherein the water-soluble hydrophilic polymer polymericmaterial having epoxide groups comprises from about 20% to about 95% byweight of first polymer chains derived from the first multi-armpolyethyleneglycol having terminal epoxide groups and from about 5% toabout 80% by weight of hydrophilic moieties or second polymer chainsderived from said at least one hydrophilicity-enhancing agent having atleast one reactive functional group selected from the group consistingof amino group, carboxyl group, hydroxyl, thiol group, and combinationthereof.
 5. The method of claim 4, wherein at least one of the first andsecond hydrophilicity-enhancing agents is selected from the groupconsisting of amino-containing monosaccharides; carboxyl- containingmonosaccharides; thiol-containing monosaccharides; amino-containingdisaccharides; carboxyl-containing disaccharides; thiol-containingdisaccharides; amino-containing oligosaccharides; carboxyl-containingoligosaccharides; thiol-containing oligosaccharides; and combinationsthereof.
 6. The method of claim 4, wherein at least one of the first andsecond hydrophilicity-enhancing agents is a hydrophilic polymer havingone or more amino, carboxyl and/or thiol groups, wherein the content ofmonomeric units having an amino (—NHR′ with R′ as defined above),carboxyl (—COOH) and/or thiol (—SH) group in the hydrophilic polymer asa hydrophilicity-enhancing agent is less than about 40% by weight basedon the total weight of the hydrophilic polymer.
 7. The method of claim4, wherein at least one of the first and second hydrophilicity-enhancingagents are selected from the group consisting of carboxymethylcellulose,carboxyethylcellulose, carboxypropylcellulose, hyaluronic acid,chondroitin sulfate, and combinations thereof.
 8. The method of claim 4,wherein at least one of the first and second hydrophilicity-enhancingagents are selected from the group consisting of PEG-N H₂; PEG-SH;PEG-COOH; H₂N-PEG-NH₂; HOOC-PEG-COOH; HS-PEG-SH; H₂N-PEG-COOH;HOOC-PEG-SH; H₂N-PEG-SH; multi-arm PEG with at least one amino group;multi-arm PEG with at least one carboxyl group; multi-arm PEG with atleast one thiol group; PEG dendrimers with at least one amino group; PEGdendrimers with at least one carboxyl group; PEG dendrimers with atleast one thiol group; a monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated homo- or copolymer of a non-reactive hydrophilicvinylic monomer selected from the group consisting of acryamide (AAm),N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP), N-vinyl-N-methylacetamide, glycerol (meth)acrylate, hydroxyethyl (meth)acrylate,N-hydroxyethyl (meth)acrylamide, C₁-C₄-alkoxy polyethylene glycol(meth)acrylate having a weight average molecular weight of up to 400Daltons, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone,N,N-dimethylaminoethyl (meth)acrylate, N,N-dimethylaminopropyl(metha)crylamide, (meth)acryloyloxyethyl phosphorylcholine, andcombinations thereof; a copolymer which is a polymerization product of acomposition comprising (1) from about 0.1% to about 30% by weight of(meth)acrylic acid, C₂-C₁₂ alkylacrylic acid, vinylamine, allylamineand/or amino-C₂-C₄ alkyl (meth)acrylate, and (2) (meth)acryloyloxyethylphosphorylcholine and/or at least one non-reactive hydrophilic vinylicmonomer selected from the group consisting of acryamide,N,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinyl-N-methyl acetamide,glycerol (meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl(meth)acrylamide, C₁-C₄-alkoxy polyethylene glycol (meth)acrylate havinga weight average molecular weight of up to 400 Daltons, vinyl alcohol,and combination thereof.
 9. The method of claim 1, wherein the packagingsolution comprises a mixture of a third multi-arm polyethyleneglycolhaving terminal epoxide groups and a second hydrophilicity-enhancingagent having at least one reactive functional group selected from thegroup consisting of amino group, carboxyl group, hydroxyl group, thiolgroup, and combination thereof.
 10. The method of claim 9, wherein atleast one of the first and second hydrophilicity-enhancing agents isselected from the group consisting of amino-containing monosaccharides;carboxyl- containing monosaccharides; thiol-containing monosaccharides;amino-containing disaccharides; carboxyl-containing disaccharides;thiol-containing disaccharides; amino-containing oligosaccharides;carboxyl-containing oligosaccharides; thiol-containing oligosaccharides;and combinations thereof.
 11. The method of claim 9, wherein at leastone of the first and second hydrophilicity-enhancing agents is ahydrophilic polymer having one or more amino, carboxyl and/or thiolgroups, wherein the content of monomeric units having an amino (—NHR′with R′ as defined above), carboxyl (—COOH) and/or thiol (—SH) group inthe hydrophilic polymer as a hydrophilicity-enhancing agent is less thanabout 40% by weight based on the total weight of the hydrophilicpolymer.
 12. The method of claim 9, wherein at least one of the firstand second hydrophilicity-enhancing agents are selected from the groupconsisting of carboxymethylcellulose, carboxyethylcellulose,carboxypropylcellulose, hyaluronic acid, chondroitin sulfate, andcombinations thereof.
 13. The method of claim 9, wherein at least one ofthe first and second hydrophilicity-enhancing agents are selected fromthe group consisting of PEG-N H₂; PEG-SH; PEG-COOH; H₂N-PEG-NH₂;HOOC-PEG-COOH; HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH; H₂N-PEG-SH;multi-arm PEG with one or more amino, carboxyl or thiol groups; PEGdendrimers with one or more amino, carboxyl or thiol groups; amonoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- orcopolymer of a non-reactive hydrophilic vinylic monomer selected fromthe group consisting of acryamide (AAm), N,N-dimethylacrylamide (DMA),N-vinylpyrrolidone (NVP), N-vinyl-N-methyl acetamide, glycerol(meth)acrylate, hydroxyethyl (meth)acrylate, N-hydroxyethyl(meth)acrylamide, C₁-C₄-alkoxy polyethylene glycol (meth)acrylate havinga weight average molecular weight of up to 400 Daltons, vinyl alcohol,N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, N,N-dimethylaminoethyl(meth)acrylate, N,N-dimethylaminopropyl (metha)crylamide,(meth)acryloyloxyethyl phosphorylcholine, and combinations thereof; acopolymer which is a polymerization product of a composition comprising(1) from about 0.1% to about 30% by weight of (meth)acrylic acid, C₂-C₁₂alkylacrylic acid, vinylamine, allylamine and/or amino-C₂-C₄ alkyl(meth)acrylate, and (2) (meth)acryloyloxyethyl phosphorylcholine and/orat least one non-reactive hydrophilic vinylic monomer selected from thegroup consisting of acryamide, N,N-dimethylacrylamide,N-vinylpyrrolidone, N-vinyl-N-methyl acetamide, glycerol (meth)acrylate,hydroxyethyl (meth)acrylate, N-hydroxyethyl (meth)acrylamide, C₁-C₄-alkoxy polyethylene glycol (meth)acrylate having a weight averagemolecular weight of up to 400 Daltons, vinyl alcohol, and combinationthereof.
 14. The method of claim 2, wherein the packaging solutioncomprises a second multi-arm polyethyleneglycol having terminal epoxidegroups.
 15. The method of claim 4, wherein the carboxyl-containingpolymeric material is: a homopolymer of a carboxyl-containing vinylicmonomer; a copolymer of two or more carboxyl-containing vinylicmonomers; a copolymer of a carboxyl-containing vinylic monomer with oneor more vinylic monomers; a carboxyl-containing cellulose; poly(glutamicacid); poly(aspartic acid); or combinations thereof, wherein thecarboxyl-containing vinylic monomer is selected from the groupconsisting of acrylic acid, a C₁-C₄ alkylacrylic acid,N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic acid),alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid,angelic acid, cinnamic acid, 1-carobxy-4-phenyl butadiene-1,3, itaconicacid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid,maleic acid, fumaric acid, and combination thereof, wherein thenon-reactive hydrophilic vinylic monomer is selected from the groupconsisting of acrylamide (AAm), methacrylamide N,N-dimethylacrylamide(DMA), N,N-dimethylmethacrylamide (DMMA), N-vinylpyrrolidone (NVP),N,N,-dimethylaminoethylmethacrylate (DMAEM),N,N-dimethylaminoethylacrylate (DMAEA),N,N-dimethylaminopropylmethacrylamide (DMAPMAm),N,N-dimethylaminopropylacrylamide (DMAPAAm), glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate,C₁-C₄-alkoxy polyethylene glycol (meth)acrylate having a weight averagemolecular weight of up to 1500 Daltons, N-vinyl formamide, N-vinylacetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allylalcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in thecopolymer), a phosphorylcholine-containing vinylic monomer, andcombinations thereof.
 16. The method of claim 9, wherein thecarboxyl-containing polymeric material is: a homopolymer of acarboxyl-containing vinylic monomer; a copolymer of two or morecarboxyl-containing vinylic monomers; a copolymer of acarboxyl-containing vinylic monomer with one or more vinylic monomers; acarboxyl-containing cellulose; poly(glutamic acid); poly(aspartic acid);or combinations thereof, wherein the carboxyl-containing vinylic monomeris selected from the group consisting of acrylic acid, a C₁-C₄alkylacrylic acid, N,N-2-acrylamidoglycolic acid, beta methyl-acrylicacid (crotonic acid), alpha-phenyl acrylic acid, beta-acryloxy propionicacid, sorbic acid, angelic acid, cinnamic acid, 1-carobxy-4-phenylbutadiene-1,3, itaconic acid, citraconic acid, mesaconic acid,glutaconic acid, aconitic acid, maleic acid, fumaric acid, andcombination thereof, wherein the non-reactive hydrophilic vinylicmonomer is selected from the group consisting of acrylamide (AAm),methacrylamide N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide(DMMA), N-vinylpyrrolidone (NVP), N,N,-dimethylaminoethylmethacrylate(DMAEM), N,N-dimethylaminoethylacrylate (DMAEA),N,N-dimethylaminopropylmethacrylamide (DMAPMAm),N,N-dimethylaminopropylacrylamide (DMAPAAm), glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1- methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl (meth)acrylate, hydroxypropyl (meth)acrylate,C₁-C₄-alkoxy polyethylene glycol (meth)acrylate having a weight averagemolecular weight of up to 1500 Daltons, N-vinyl formamide, N-vinylacetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allylalcohol, vinyl alcohol (hydrolyzed form of vinyl acetate in thecopolymer), a phosphorylcholine-containing vinylic monomer, andcombinations thereof.
 17. The method of claim 16, wherein thecarboxyl-containing polymeric material is polyacrylic acid,polymethacrylic acid, poly(C₂-C₁₂ alkylacrylic acid), poly[acrylicacid-co-methacrylic acid], poly(N,N-2-acrylamidoglycolic acid),poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylicacid-co-vinylpyrrolidone], poly[C₂-C₁₂ alkylacrylic acid-co-acrylamide],poly[C₂-C₁₂ alkylacrylic acid-co-vinyl pyrrolidone], hydrolyzedpoly[(meth)acrylic acid-co-vinylacetate], hydrolyzed poly[C₂-C₁₂alkylacrylic acid-co-vinylacetate], polyethyleneimine (PEI),polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylaminehomo- or copolymer, or combinations thereof.
 18. The method of claim 16,wherein the weight average molecular weight M_(w) , of thecarboxyl-containing polymeric material is at least about 10,000 Daltons.19. The method of claim 1, wherein the step (b) is performed by dippingthe silicone hydrogel contact lens in a solution of thecarboxyl-containing polymeric material, wherein the solution is preparedby dissolving the carboxyl-containing polymeric material in a mixture ofwater and one or more organic solvents, an organic solvent, or a mixtureof one or more organic solvent.